dbSNP rs941389: UGT2B4:c.44-613T>G (chr4-69496023-A-C) – ACMG Classification: Benign (-12 pts)

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_StrongBA1

The NM_001297616.2(UGT2B4):c.44-613T>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.357 in 1,237,918 control chromosomes in the GnomAD database, including 80,331 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: 𝑓 0.34 ( 8720 hom., cov: 32)

Exomes 𝑓: 0.36 ( 71611 hom. )

Consequence

UGT2B4
NM_001297616.2 intron

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -0.414

Publications

6 publications found

Variant links:

COSMIC-nc: COSV59315927

Genes affected

UGT2B4 (HGNC:12553): (UDP glucuronosyltransferase family 2 member B4) Enables glucuronosyltransferase activity. Involved in cellular glucuronidation and estrogen metabolic process. Predicted to be located in endoplasmic reticulum membrane. Predicted to be integral component of membrane. Predicted to be active in intracellular membrane-bounded organelle. [provided by Alliance of Genome Resources, Apr 2022]

UGT2B4 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -12 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.84).

BA1

GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.37 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	Effect	Exon rank	MANE	Protein	UniProt
UGT2B4	NM_001297616.2 link	c.44-613T>G	intron_variant	Intron 1 of 6		NP_001284545.1	P06133-2
UGT2B4	NM_021139.3 link	c.-162T>G	upstream_gene_variant		ENST00000305107.7	NP_066962.2	P06133-1
UGT2B4	NM_001297615.2 link	c.-162T>G	upstream_gene_variant			NP_001284544.1	P06133-3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
UGT2B4	ENST00000305107.7 link	c.-162T>G		upstream_gene_variant		1	NM_021139.3	ENSP00000305221.6		P06133-1

Frequencies

GnomAD3 genomes

AF:

0.337

AC:

51159

AN:

151888

Hom.:

8724

Cov.:

show subpopulations

Gnomad AFR

AF:

0.296

Gnomad AMI

AF:

0.338

Gnomad AMR

AF:

0.311

Gnomad ASJ

AF:

0.345

Gnomad EAS

AF:

0.258

Gnomad SAS

AF:

0.363

Gnomad FIN

AF:

0.324

Gnomad MID

AF:

0.345

Gnomad NFE

AF:

0.373

Gnomad OTH

AF:

0.340

GnomAD4 exome

AF:

0.359

AC:

390201

AN:

1085912

Hom.:

71611

AF XY:

0.359

AC XY:

191799

AN XY:

533812

show subpopulations

African (AFR)

AF:

0.298

AC:

7098

AN:

23812

American (AMR)

AF:

0.291

AC:

5810

AN:

19948

Ashkenazi Jewish (ASJ)

AF:

0.342

AC:

5825

AN:

17034

East Asian (EAS)

AF:

0.221

AC:

7481

AN:

33786

South Asian (SAS)

AF:

0.365

AC:

17371

AN:

47568

European-Finnish (FIN)

AF:

0.320

AC:

10539

AN:

32978

Middle Eastern (MID)

AF:

0.342

AC:

1603

AN:

4690

European-Non Finnish (NFE)

AF:

0.370

AC:

318351

AN:

859840

Other (OTH)

AF:

0.349

AC:

16123

AN:

46256

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.507

Heterozygous variant carriers

11588

23176

34763

46351

57939

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

10144

20288

30432

40576

50720

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.337

AC:

51175

AN:

152006

Hom.:

8720

Cov.:

AF XY:

0.332

AC XY:

24680

AN XY:

74290

show subpopulations

African (AFR)

AF:

0.295

AC:

12245

AN:

41472

American (AMR)

AF:

0.311

AC:

4739

AN:

15260

Ashkenazi Jewish (ASJ)

AF:

0.345

AC:

1195

AN:

3466

East Asian (EAS)

AF:

0.258

AC:

1335

AN:

5168

South Asian (SAS)

AF:

0.362

AC:

1747

AN:

4826

European-Finnish (FIN)

AF:

0.324

AC:

3417

AN:

10558

Middle Eastern (MID)

AF:

0.347

AC:

102

AN:

294

European-Non Finnish (NFE)

AF:

0.373

AC:

25368

AN:

67936

Other (OTH)

AF:

0.340

AC:

719

AN:

2114

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.501

Heterozygous variant carriers

1709

3418

5126

6835

8544

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

518

1036

1554

2072

2590

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.345

Hom.:

2847

Bravo

AF:

0.333

Asia WGS

AF:

0.314

AC:

1085

AN:

3458

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.84

CADD

Benign

0.23

(source)

DANN

Benign

0.39

PhyloP100

-0.41

PromoterAI

-0.040

Neutral

(source)

Mutation Taster

=100/0

polymorphism (auto)

(source)

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over